Tay Sachs Disease Flashcards
A 6-month-old boy is brought to the pediatrician due to progressive motor weakness and failure to meet developmental milestones. His parents state that he was previously developing normally but has recently lost the ability to roll over and sit unsupported. On examination, the child has hyperreflexia, an exaggerated startle response, and a cherry-red macula. There is no hepatosplenomegaly. Which of the following best explains the underlying cause of this condition?
A) Deficiency of hexosaminidase A
B) Deficiency of sphingomyelinase
C) Deficiency of β-glucosidase
D) Deficiency of α-galactosidase A
E) Deficiency of arylsulfatase A
Answer: Deficiency of hexosaminidase A
Explanation: Tay-Sachs Disease is an autosomal recessive lysosomal storage disorder caused by a deficiency of hexosaminidase A, leading to the accumulation of GM2 ganglioside in neurons. The condition is characterized by progressive neurodegeneration, developmental delay, hyperacusis (exaggerated startle response), and a cherry-red macula without hepatosplenomegaly. It is common in the Ashkenazi Jewish population. Diagnosis is confirmed with enzyme assay showing reduced hexosaminidase A activity.
Incorrect Answers:
B) Deficiency of sphingomyelinase causes Niemann-Pick disease, which also presents with a cherry-red macula but is associated with hepatosplenomegaly and foam cells.
C) Deficiency of β-glucosidase (glucocerebrosidase) causes Gaucher disease, characterized by hepatosplenomegaly, pancytopenia, and bone pain without neurodegeneration.
D) Deficiency of α-galactosidase A causes Fabry disease, presenting with acroparesthesia, angiokeratomas, and renal or cardiac complications.
E) Deficiency of arylsulfatase A causes metachromatic leukodystrophy, a disorder of myelin metabolism with progressive motor and cognitive dysfunction.
What is the genetic inheritance pattern of Tay-Sachs Disease?
Autosomal recessive inheritance
What enzyme deficiency causes Tay-Sachs Disease?
Deficiency of hexosaminidase A
What substrate accumulates in Tay-Sachs Disease?
Accumulation of GM2 ganglioside in lysosomes
What are the clinical features of Tay-Sachs Disease?
- Progressive neurodegeneration
- Impaired startle response
- developmental delay
- hyperreflexia
- hyperacusis
- cherry-red macula
What is the characteristic ocular finding in the fundus in Tay-Sachs Disease?
Cherry-red macula with no hepatosplenomegaly
What distinguishes Tay-Sachs Disease from Niemann-Pick Disease?
Tay-Sachs lack hepatosplenomegaly
Niemann-Pick does
What populations are at higher risk of Tay-Sachs Disease?
Ashkenazi Jewish population
How is Tay-Sachs Disease diagnosed?
Enzyme assay showing reduced hexosaminidase A activity; genetic testing
What is the typical progression of Tay-Sachs Disease?
Rapid neurodegeneration with loss of motor skills and death by age 3-5
What is the treatment for Tay-Sachs Disease?
Supportive care; there is no cure for Tay-Sachs Disease
What is the most common cause of death in Tay-Sachs Disease?
Usually, patients die of respiratory infections before 5 years of age.
